SR141716A is an inverse agonist at the human cannabinoid CB 1 receptor

Abstract

The effects of R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3- de]-1,4-benzoxazin-yl]-(1-napthalenyl)methanone mesylate (WIN 55,212-2) and N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A) on guanosine-5′- O-(3-[ 35 S ]thio)triphosphate ([ 35 S ]GTP γS) binding to membranes isolated from human cannabinoid CB 1 receptor-transfected Chinese hamster ovary (CHO) cells were examined. WIN 55,212-2 stimulated [ 35 S ]GTP γS binding 76.3% above basal levels whereas SR141716A produced a 22.3% decrease in basal [ 35 S ]GTP γS binding. These findings demonstrate that WIN 55,212-2 is an agonist and SR141716A is an inverse agonist in this system.